title: Association of the Q121 variant of ENPP1 gene with decreased kidney function among patients with type 2 diabetes.
abstract: BACKGROUND
  Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D.
  
  
  METHODS
  The ENPP1 Q121 variant.
  
  
  METHODS
  Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A(1c), triglycerides, total cholesterol, and high-density lipoprotein cholesterol.
  
  
  RESULTS
  Decreased GFRs (ie, estimated GFR <60 mL/min/1.73 m(2)).
  
  
  RESULTS
  In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals (P = 0.04).
  
  
  CONCLUSIONS
  P values not approaching a genome-wide level of significance.
  
  
  CONCLUSIONS
  Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.
authors.affiliation: Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. sdecosm@tin.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.forename: Antonio
authors.initials: A
authors.lastname: Minenna
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Ryan
authors.initials: R
authors.lastname: Thompson
authors.forename: Robert
authors.initials: R
authors.lastname: Thompson
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Miscio
authors.forename: Monica
authors.initials: M
authors.lastname: Vedovato
authors.forename: Anna
authors.initials: A
authors.lastname: Rauseo
authors.forename: Alois
authors.initials: A
authors.lastname: Saller
authors.forename: Sandra
authors.initials: S
authors.lastname: Mastroianno
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Roberto
authors.initials: R
authors.lastname: Trevisan
authors.forename: Paola
authors.initials: P
authors.lastname: Fioretto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D000419:Albuminuria; D019943:Amino Acid Substitution; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases